How Stress Fuels Depression

Stress can lead to depression. But a new study has found that the brain can buffer the effect.

It was once thought that the brain was incapable of making new brain cells (neurons) in adulthood. But more and more, research is finding that the brain is actually much more dynamic and plastic – capable of change – than once believed. Now, a new study shows how neurogenesis, the birth of new neurons, is responsible for "buffering" the stress response, and preventing it from triggering full-blown depression.

Many people are familiar with the idea that stress and depression are intimately connected, and that the one may lead to the other. Earlier studies have shown that stress and the hormones involved in the stress response dampen the rate of neurogenesis in a brain area called the hippocampus. This area helps govern the stress response, but is also known to be involved in learning and memory. Furthermore, it’s thought that both exercise and antidepressant medications like SSRIs help conquer depression by enhancing the rate of neurogenesis.

This study is impressive because it illustrates the vicious cycle that defines the stress-neurogenesis connection: stress can reduce the number of new neurons formed in the brain, but new neurons are required to rebound from stressful experiences.

The team of researchers was able to halt the production of new neurons in the brains of mice, in one of two ways: using genetic techniques or radiation. They subjected the mice to stress by restraining them physically. Just after the restraint, the mice who could not produce new neurons and normal mice had similarly heightened levels of the stress hormone corticosterone (the mouse equivalent to our stress hormone, cortisol). But half an hour later, stress hormones of the normal mice had returned to normal, but those of the neurogenesis-incapable mice were still elevated. This suggests that the ability to generate new neurons is at least in part what underlies the brain’s recovery from stress.

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The authors further showed that after being stressed, mice without the capacity for neurogenesis were less likely to take a "risk" in venturing out into an open space to get food. This reluctance to explore new environs mirrors the behavior of many depressed individuals, who are less likely to break out of old behavior patterns and try new things than non-depressed people. The normal mice, as you might guess, scampered out into the open space to claim the snack.

This study is impressive because it illustrates the vicious cycle that defines the stress-neurogenesis connection: stress can reduce the number of new neurons formed in the brain, but new neurons are required to rebound from stressful experiences. Though this is a somewhat disheartening reality, understanding how this circuitry works is crucial in finding new ways to treat major depression, which affects around 15% of people at some point in their lives. The coming years will, no doubt, bring a deeper understanding of what’s going on in the depressed brain, along with innovative new treatments.

The research was carried out by a team at NIH’s National Institutes of Mental Health in Bethesda, MD, and published in the August 3, 2011 online issue of Nature.